Eleanor Hill Venning
Dr. Eleanor Hill Venning, c. 1962. Photograph from Endocrinology 71, iss.1 (1962). (courtesy of the Endocrine Society). Image Source: The Canadian Encyclopedia, digitally edited.
Jerilynn C. Prior BA, MD, FRCPC, Professor Emerita, Endocrinology/Medicine University of British Columbia
It was 1937, during the “great depression,” when a young woman published a paper describing the complex chemical recipe for measuring progesterone in urine. That woman was Canadian pioneer scientist, Dr. Eleanor Hill Venning. I ruefully admit that I had never heard of her until I was recently invited to “fact-check” an entry in the Canadian Encyclopedia. But I have used her urine progesterone measurement in studies of women’s experiences changes during the menstrual cycle1.
What is important about Venning’s discovery?
Venning’s publication showed for the first time that a hormone level could actually be measured. The only hormone assessments at the time were bioassays, meaning uterine size changes in a laboratory rat when a human’s blood was injected. Also, in the 1930s, few women got bachelor’s degrees, much less doctorates. And, like today, fewer women than men elected to study in the fields of basic science and math. Furthermore, she must have been a very quick study because she published her article showing how to measure urine pregnanediol glucuronide (commonly called PdG), only four years after she got her PhD.
A year later, in 1938 Venning reported having done over 2000 PdG assays. Remarkably she had tracked eight women across an entire pregnancy; results showed how progesterone levels increased to their peak just before delivery. Here is her original diagram.
The world of the 1930s was fascinated by “hormones”. These were chemicals made in one part of the body that had mysterious effects at far-flung places. Estrone, the menopausal form of estrogen, was chemically characterized in 1929 by scientists in both Germany and the United States. But estrone could be assessed only by bioassay. It was not until the 1960s, following the work of NY City scientist, Dr. Rosalyn Yalow, that hormones could be measured in blood by a process called radio-immunoassay that is still often used today.
How did Venning learn the practical importance of her discovery?
Eleanor Venning was a scientist at McGill University (known as “the Harvard of the North”); its medical school was the alma mater of Sir William Osler, who came to be considered “The Father of Modern Medicine.” New knowledge was created because scientists at McGill worked closely with physicians at Montreal’s Royal Victoria Hospital. In particular, Venning worked with J.S.L. Browne MD, and it was with him (1937) that she showed that urine progesterone levels increased during the menstrual cycle only after an egg had been released from the ovary. Together with others in Montreal, Venning and Browne were part of the creation of the new medical discipline, endocrinology.
Despite being highly reputable, McGill University School of Medicine in the 1930s had few women scientists or physicians; fewer still went on to faculty leadership positions. Thus, it is remarkable that Dr. Venning later became Professor and Head of Experimental Medicine at McGill University and the Director of the Endocrine Laboratories at Royal Victoria Hospital.
Is Venning’s new PdG method important today?
Yes. Many important published studies have measured PdG to assess ovulation. Also, many menstrual cycle apps such as MiraÒ2 and PremomÒ, also use urine PdG measurements. Although initially Venning measured PdG in 24-hour urines, currently a spot morning urine is sufficient since the assay has been made more sensitive and specific.
With this more sensitive PdG assay, physicians discovered that it was measurable across the whole menstrual cycle. Why? Because the adrenal gland makes low levels of progesterone in men and children as well as in women of all ages.
One of the key studies made possible by urine PdG was the Daily Hormone3 Sub-study done within a huge and long USA study of perimenopause called “Study of Women Across the Nation (or SWAN).” SWAN enrolled over 16,000 women of African-American, Chinese, Japanese and White ethnicities across the US. After documenting other things, SWAN investigator, Dr. Nanette Santoro asked: “How does ovulation change across perimenopause?” To answer, PdG was assessed daily every year by over 800 women across one cycle or for 50 days for three years. Results showed that even in cycles that appeared to be ovulatory (by three expert’s assessment of basal body temperature records, a surprising ovulation “gold standard”), PdG levels gradually decreased across perimenopause. In addition, the closer women were to menopause the less likely they were to ovulate at all.
What new information have we learned about PdG?
I mentioned earlier, I designed a study to assess whether “molimina”, normal premenstrual women’s experiences, was associated with ovulation using daily Menstrual Cycle Diary© records and urine for PdG twice a week across a full cycle1. To our surprise, there was no standard PdG level at which we could say all cycles were ovulatory. Instead, each woman’s basal PdG level during the cycle’s first week and a half, needed to be multiplied by three to provide levels above which her cycle was to be ovulatory 4.
Why was PdG so variable between people? Because the activity of the metabolic enzyme (called CYP3A4) that allows excretions of steroid hormones such as progesterone and cortisol, is different in different people. At the time we also learned that likely ethnic CYP3A4 differences occurred between White and Chinese people5.
Canadian scientist Dr. Eleanor Venning changed our understanding—we celebrate her life and work.
Note: If you wish to read more about Dr. Eleanor H. Venning, here is her obituary.
Reference List
- Prior JC, Konishi C, Hitchcock CL, et al. Does Molimina Indicate Ovulation? Prospective Data in a Hormonally Documented Single-Cycle in Spontaneously Menstruating Women. Int J Env Res Pub He 2018;15(5) (ijerph15051016 pii ;10.3390/ijerph15051016 doi). DOI: 10.3390/ijerph15051016.
- Bouchard T, P. Y, Doyle-Baker P. Establishing a Gold Standard for Quantitative Menstrual Cycle Monitoring. Medicina 2023;59(9). DOI: 10.3390/medicina59091513.
- Santoro N, El Khoudary SR, Nasr A, et al. Daily luteal serum and urinary hormone profiles in the menopause transition: Study of Women’s Health Across the Nation. Menopause 2020;27(2):127-133. DOI: 10.1097/GME.0000000000001453.
- Kassam A, Overstreet JW, Gold EB, Lasley BL. A simple algorithim using daily urinary pregnanediol-3-glucuronide to evaluate luteal phase progesterone production. SocGynecolInvest 1994;210:P31-P31.
- Lin Y, Anderson GD, Kantor E, Ojemann LM, Wilensky AJ. Differences in the urinary excretion of 6-beta-hydroxycortisol/cortisol between Asian and Caucasian women. J ClinPharmacol 1999;39(6):578-582. (PM:10354961).